Is CHD4 p.Pro481fs (c.1442del) pathogenic?

CHD4 p.Pro481fs (c.1442del) is classified Uncertain significance in CHD4 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-01-18). No gnomAD frequency available for this variant; Associated with Sifrim-Hitz-Weiss syndrome.

What condition is associated with CHD4 p.Pro481fs (c.1442del)?

CHD4 p.Pro481fs (c.1442del) is associated with Sifrim-Hitz-Weiss syndrome (ClinVar).

How common is CHD4 p.Pro481fs (c.1442del) in the general population?

CHD4 p.Pro481fs (c.1442del) is no gnomAD frequency available for this variant (gnomAD).

How is CHD4-related neurodevelopmental disorder inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CHD4 p.Pro481fs

c.1442del · rs2136222835 · VCV1697098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Sifrim-Hitz-Weiss syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.2	GERP -3.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD4
Protein: p.Pro481fs
Coding: c.1442del
MANE Select: NM_001273
dbSNP: rs2136222835
Type: Deletion
Location: chr12:6599813 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.41 · 12 PDB

Full CHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Sifrim-Hitz-Weiss syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CHD4-related neurodevelopmental disorder (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

Similar variants

CHD4 p.Leu1219fs Pathogenic ★ same condition
CHD4 p.Asn1362_Asp1365del Uncertain significance ★ same condition
CHD4 p.Gln542fs Uncertain significance ★ same condition
CHD4 p.Arg1068His Pathogenic/Likely pathogenic ★★ same condition
CHD4 p.Arg1173Gln Pathogenic/Likely pathogenic ★★ same condition
CHD4 p.Arg1173Trp Pathogenic/Likely pathogenic ★★ same condition
CHD4 p.Arg1177Cys Pathogenic/Likely pathogenic ★★ same condition
CHD4 p.Arg1183Cys Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chd4-p-pro481fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown